Durable efficacy of risankizumab through week 148 in patients with moderate-To-severe crohn's disease: A post hoc analysis of part 2 of the sequence study

Abstract

Background: Many patients (pts) with Crohn's disease (CD) lose treatment response over time, underscoring the importance of treatments with sustained efficacy. Risankizumab (RZB) has previously shown durable clinical and endoscopic efficacy in pts with moderate-To-severe CD.1,2 Here, we continued to assess the durability of RZB efficacy in pts with moderate-To-severe CD and prior anti-TNF failure through 3 years of treatment in the ongoing SEQUENCE study. Method(s): In SEQUENCE (NCT04524611), pts randomised to RZB in Part 1 (the 48-week wk] head-To-head study versus ustekinumab) who completed the wk 48 visit could receive open label maintenance RZB 360 mg SC every 8 wks during Part 2 starting at wk 52.3,4 In this post hoc analysis, durability of efficacy was defined as the proportion of pts among those who achieved clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS) at wks 8 or 48, or endoscopic response, endoscopic remission, or mucosal healing at wks 24 or 48, that subsequently achieved the respective endpoint at later assessed timepoints. Pts with inadequate response to treatment could receive RZB rescue therapy. Details of RZB rescue therapy and endpoint definitions are provided in the Figure footnotes. Clinical assessments were performed post-baseline at wk 8, wk 24, and every 24 wks thereafter. Endoscopic assessments were performed post-baseline at wks 24, 48 and 148. Data included all intent-To-Treat pts who received at least one dose of RZB in Part 2 and were summarised as observed (AO) and using modified nonresponder imputation (mNRI). Safety has been reported previously.4 Results: A total of 224 pts entered Part 2 and, per AO data, most pts who achieved clinical remission at wk 8 maintained clinical remission throughout later timepoints (Figure 1); clinical remission at wk 148 was achieved by 98.5% (CDAI) and 88.1% (SF/APS) of wk 8 clinical remitters. Durability of clinical remission was also observed throughout later timepoints in pts who achieved clinical remission at wk 48. Of pts who achieved endoscopic response, endoscopic remission, or mucosal healing at wk 24, 84.7%, 78.2%, and 67.3% of pts, respectively, maintained the corresponding endpoint at wk 148; similar results at wk 148 were observed for pts who achieved these endoscopic endpoints at wk 48 (Figure 2). Data analysed using mNRI showed similar results to AO data. Conclusion(s): Pts with moderate-To-severe CD and prior anti-TNF failure, a population generally considered to be more refractory, demonstrated durable clinical remission, endoscopic response, endoscopic remission, and mucosal healing through 148 wks of RZB treatment in the SEQUENCE study.